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Junyu Liu,1,* Li Zhang,2,* Xiaoyu Zhou,1 Yingge Yue,1 Wenjin He,2 Keming Yun,3 Xiangyu Wang,1 Wei Bian2 1Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, People’s Republic of China; 2School of Basic Medical Science, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 3School of Forensic Medicine, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiangyu Wang, Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, 030000, People’s Republic of China, Email wangxiangyu76@163.com Wei Bian, School of Basic Medical Science, Shanxi Medical University, Taiyuan, Shanxi, 030000, People’s Republic of China, Email weibian@sxmu.edu.cnIntroduction: Malignant tumors seriously affect people’s normal lives, but the effective treatment of cancer needs to be further improved.Methods: In this study, we prepared nanocomposites with photothermal therapy (PTT)/photodynamic therapy (PDT)/chemodynamic therapy (CDT) properties named Fe2O3/GCN/ICG/DHA. Under high H2O2 conditions, Fe3+ is reduced to Fe2+ and reacts with DHA to produce C-center free radicals, which kill tumor cells. In addition, ICG produced a warming effect and cytotoxic singlet oxygen with 808 nm laser irradiation.Results: The significant combined antitumor activity of Fe2O3/GCN/ICG/DHA, validated in vitro and in vivo, provides strong experimental support for advancing this transition metal iron-based nanocomplex towards tumor therapy applications.Discussion: It expands the potential applications of novel nanocomplex in the field of tumor therapy. Keywords: nanocomplexes, malignant tumors, chemodynamic therapy, photothermal therapy, photodynamic therapy

Combined chemo/chemodynamic therapy is a promising strategy to achieve an improved anticancer effect. However, the hypoxic microenvironment and limited amount of H2O2 in most solid tumors severely restrict the efficacy of this treatment. Herein, the construction of a nanocatalytic medicine, CaO2@DOX@ZIF‐67, via a bottom‐up approach is described. CaO2@DOX@ZIF‐67 simultaneously supplies O2 and H2O2 to achieve improved chemo/chemodynamic therapy. In the weakly acidic environment within tumors, CaO2@DOX@ZIF‐67 is broken down to rapidly release the Fenton‐like catalyst Co2+ and the chemotherapy drug doxorubicin (DOX). The unprotected CaO2 reacts with H2O to generate both O2 and H2O2. The generated O2 relieves the hypoxia in the tumor and further improve the efficacy of DOX. Meanwhile, the generated H2O2 reacts with Co2+ ions to produce highly toxic •OH through a Fenton‐like reaction, resulting in improved chemodynamic therapy. The hypoxic microenvironment and limited amount of H2O2 in most solid tumors severely restrict the efficacy of chemotherapy and chemodynamic therapy, respectively. Herein, a nanocatalytic medicine, CaO2@DOX@ZIF‐67, is synthesized via a bottom‐up approach. By virtue of simultaneously producing O2 and H2O2 under acidic conditions, the fabricated nanocatalytic medicine can eliminate hypoxic tumors via enhanced chemo/chemodynamic therapy.

The incorporation of new modalities into chemotherapy greatly enhances the anticancer efficacy combining the merits of each treatment, showing promising potentials in clinical translations. Herein, a hybrid nanomedicine (Au/FeMOF@CPT NPs) is fabricated using metal–organic framework (MOF) nanoparticles and gold nanoparticles (Au NPs) as building blocks for cancer chemo/chemodynamic therapy. MOF NPs are used as vehicles to encapsulate camptothecin (CPT), and the hybridization by Au NPs greatly improves the stability of the nanomedicine in a physiological environment. Triggered by the high concentration of phosphate inside the cancer cells, Au/FeMOF@CPT NPs effectively collapse after internalization, resulting in the complete drug release and activation of the cascade catalytic reactions. The intracellular glucose can be oxidized by Au NPs to produce hydrogen dioxide, which is further utilized as chemical fuel for the Fenton reaction, thus realizing the synergistic anticancer efficacy. Benefitting from the enhanced permeability and retention effect and sophisticated fabrications, the blood circulation time and tumor accumulation of Au/FeMOF@CPT NPs are significantly increased. In vivo results demonstrate that the combination of chemotherapy and chemodynamic therapy effectively suppresses the tumor growth, meantime the systemic toxicity of this nanomedicine is greatly avoided. A hybrid nanomedicine (Au/FeMOF@CPT NPs) consisting of metal–organic framework nanoparticles (MOF NPs) and Au NPs is developed for cancer chemo/chemodynamic therapy. MOF NPs are used as vehicles to encapsulate camptothecin (CPT). H2O2 from the oxidation of intracellular glucose by Au NPs is further utilized as fuel for the Fenton reaction, thus realizing the synergistic anticancer efficacy.

Overproduction of reactive oxygen species (ROS), metal ion accumulation, and tricarboxylic acid cycle collapse are crucial factors in mitochondria‐mediated cell death. However, the highly adaptive nature and damage‐repair capabilities of malignant tumors strongly limit the efficacy of treatments based on a single treatment mode. To address this challenge, a self‐reinforced bimetallic Mito‐Jammer is developed by incorporating doxorubicin (DOX) and calcium peroxide (CaO2) into hyaluronic acid (HA) ‐modified metal‐organic frameworks (MOF). After cellular, Mito‐Jammer dissociates into CaO2 and Cu2+ in the tumor microenvironment. The exposed CaO2 further yields hydrogen peroxide (H2O2) and Ca2+ in a weakly acidic environment to strengthen the Cu2+‐based Fenton‐like reaction. Furthermore, the combination of chemodynamic therapy and Ca2+ overload exacerbates ROS storms and mitochondrial damage, resulting in the downregulation of intracellular adenosine triphosphate (ATP) levels and blocking of Cu‐ATPase to sensitize cuproptosis. This multilevel interaction strategy also activates robust immunogenic cell death and suppresses tumor metastasis simultaneously. This study presents a multivariate model for revolutionizing mitochondria damage, relying on the continuous retention of bimetallic ions to boost cuproptosis/immunotherapy in cancer. Self‐reinforced bimetallic Mito‐Jammer is rationally designed and synthesized by loading DOX and CaO2 into the hyaluronic acid‐modified metal‐organic framework‐199. By triggering reactive oxygen species storm and Ca2+ overload, the Mito‐Jammer could enhance the tumor‐specific Cu2+ aggregation and induce cascade mitochondrial damage to further arouse tumor‐specific cuproptosis and cuproptosis‐related immunotherapy.

The emergence of drug‐resistant bacteria poses a significant threat to people's lives and health as bacterial infections continue to persist. Currently, antibiotic therapy remains the primary approach for tackling bacterial infections. However, the escalating rates of drug resistance coupled with the lag in the development of novel drugs have led to diminishing effectiveness of conventional treatments. Therefore, the development of nonantibiotic‐dependent therapeutic strategies has become imperative to impede the rise of bacterial resistance. The emergence of chemodynamic therapy (CDT) has opened up a new possibility due to the CDT can convert H2O2 into •OH via Fenton/Fenton‐like reaction for drug‐resistant bacterial treatment. However, the efficacy of CDT is limited by a variety of practical factors. To overcome this limitation, the sterilization efficiency of CDT can be enhanced by introducing the therapeutics with inherent antimicrobial capability. In addition, researchers have explored CDT‐based combined therapies to augment its antimicrobial effects and mitigate its potential toxic side effects toward normal tissues. This review examines the research progress of CDT in the antimicrobial field, explores various strategies to enhance CDT efficacy and presents the synergistic effects of CDT in combination with other modalities. And last, the current challenges faced by CDT and the future research directions are discussed. In this review, the recent progress of CDT in the antimicrobial therapy has been introduced. Then the strategies to boost the therapeutic effect of CDT and the CDT‐based combined therapeutic strategies are outlined. Finally, the challenges and opportunities of CDT are also discussed.

Therapeutic systems to induce reactive oxygen species (ROS) have received tremendous success in the research of tumor theranostics, but suffered daunting challenges in limited efficacy originating from low presence of reactants and reaction kinetics within cancer cells. Here, ferrous sulfide‐embedded bovine serum albumin (FeS@BSA) nanoclusters, in an amorphous nature, are designed and synthesized via a self‐assembly approach. In acidic conditions, the nanoclusters degrade and simultaneously release H2S gas and Fe2+ ions. The in vitro study using Huh7 cancer cells reveals that Fe2+ released from FeS@BSA nanoclusters induces the toxic hydroxyl radical (·OH) effectively via the Fenton reaction. More interestingly, H2S gas released intracellularly presents the specific suppression effect to catalase activity of cancer cells, resulting in the promoted presence of H2O2 that facilitates the Fenton reaction of Fe2+ and consequently promotes ROS induction within the cells remarkably. After intravenous administration, the nanoclusters accumulate in the tumors of mice via the enhanced permeability and retention effect and present strong magnetic resonance imaging (MRI) signals. The findings confirm this therapeutic system can enable superior anti‐tumor performance with MRI guidance and negligible side effects. This study, therefore, offers an alternative gas‐amplified ROS‐based therapeutic platform for synergetic tumor treatment. Ferrous sulfide‐embedded bovine serum albumin (FeS@BSA) nanoclusters, in an amorphous nature, are synthesized via a self‐assembly approach. In acidic conditions, the nanoclusters degrade and simultaneously release H2S gas and Fe2+ ions. Fe2+ release effectively induces hydroxyl radical via the Fenton reaction, while intracellular H2S gas selectively suppresses catalase activity of cancer cells, enabling promoted reactive oxygen species induction and remarkable antitumor performance.

Rationale: Chemodynamic therapy (CDT) based on the Fe(II)-mediated Fenton reaction is an emerging tumor treatment strategy. However, the catalytic efficiency in tumors is crucially limited by Fe(II). Herein, an endogenous hydrogen sulfide (H2S) accelerated Fe(III)/Fe(II) transformation and photothermal synergistically enhanced CDT strategy based on ellagic acid-Fe-bovine serum albumin (EA-Fe@BSA) nanoparticles (NPs) was developed for colon tumor inhibition. On the one hand, the Fe(III) with low catalytic activity in the EA-Fe@BSA NPs could be rapidly reduced to the highly active Fe(II) by the abundant H2S in colon cancer tissues. Thus, a rapid Fe(III)/Fe(II) conversion system was established, wherein highly active Fe(II) ions were continuously regenerated to improve the CDT efficiency. On the other hand, the photothermal effect of EA-Fe@BSA NPs also accelerated the production of hydroxyl radicals (•OH), thereby synergistically enhancing the CDT performance and improving the therapeutic efficacy. Methods: The endogenous H2S accelerated Fe(III)/Fe(II) conversion and PTT enhanced CDT were investigated by characterization of the Fe valence state and detection of •OH. T1-weighted magnetic resonance imaging (MRI) was tested both in vitro and in vivo. The biocompatibility of NPs were examined via MTT assay, hemolysis analysis and routine blood measurements. The enhanced CDT was investigated in HCT116 colon cancer cells by Calcein-AM/PI staining and MTT assay, and tumor inhibition was demonstrated in HCT116 tumor bearing mice. Results: In this work, EA-Fe@BSA NPs were constructed as a CDT theranostic reagent. The H2S accelerated Fe(III)/Fe(II) conversion was confirmed, more degradation of MB and generation of •OH demonstrated the enhanced CDT in vitro. EA-Fe@BSA NPs exhibited good T1-weighted MRI performance. More importantly, it displayed strong near-infrared (NIR) absorption and excellent photothermal efficiency, further promotes the production of •OH. Hence, the efficacy of CDT was enhanced, and the tumor growth was inhibited efficiently. Conclusion: All results demonstrate that this strategy based on endogenous H2S promoted Fe(III)/Fe(II) transformation together with PTT acceleration permits efficient Fenton-reaction- mediated CDT both in vitro and in vivo, which holds great potential for effective colon cancer theranostics.

Dian-Chao Cao,1– 3,* Yan Liang,1,4,* Yang Guo,1 Dong-Yang Wu,1 Na-Na Wang,1 Yan-Mei Li,5 Hong-Fang Sun,1 Qin Wang,1 Xia Zhang,1 Yong-Liang Chi,6 Pei-Pei Sun,4 You-Jie Li,1 Ran-Ran Wang,7 Ping-Yu Wang,1,8 Shu-Yang Xie,1– 3 Ning Xie9 1Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, Shandong, 264003, People’s Republic of China; 2Department of General Surgery, the second Medical College, Yantai Affiliated Hospital, Binzhou Medical University, Yantai, Shandong, 264003, People’s Republic of China; 3Shandong Laboratory of Advanced Materials and Green Manufacturing, Yantai, Shandong, 264000, People’s Republic of China; 4Department of Oncology, Binzhou Medical University Affiliated Hospital of Traditional Chinese Medicine, Binzhou, Shandong, 256600, People’s Republic of China; 5Department of Immune Rheumatism, Yantaishan Hospital, Yantai, Shandong, 264000, People’s Republic of China; 6Department of Anesthesiology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250011, People’s Republic of China; 7Department of Rehabilitation Engineering, Institute of Rehabilitation Medicine, School of Rehabilitation Medicine, Binzhou Medical University, Yantai, Shandong, 264003, People’s Republic of China; 8Department of Epidemiology, Binzhou Medical University, Yantai, Shandong, 264003, People’s Republic of China; 9Department of Chest Surgery, Binzhou Medical University Affiliated Yantaishan Hospital, Yantai, Shandong, 264000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ning Xie, Department of Chest Surgery, Binzhou Medical University Affiliated Yantaishan Hospital, Yantai, Shandong, 264000, People’s Republic of China, Tel +86-0535-6913211, Fax +86 0535 6913163, Email sunnyvvv@163.com Shu-Yang Xie, Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, Shandong, 264003, People’s Republic of China, Tel +86 0535 6913211, Fax +86 0535 6913163, Email xieshuyang@bzmc.edu.cnPurpose: This study aims to develop an innovative delivery system, (Q+M/MnOx)@Clip, to enhance the bioavailability and therapeutic efficacy of quercetin both in tumor treatment and pain alleviation.Methods: The (Q+M/MnOx)@Clip system was evaluated to enhance the release of quercetin, investigate its ability to target cancer cells, alleviate tumor hypoxia, and improve the efficacy of chemodynamic therapy (CDT). Tumor hypoxia markers and immune response activation were assessed, along with the impact on pain relief biomarkers.Results: (Q+M/MnOx)@Clip successfully mitigated tumor hypoxia, facilitated controlled Q release, and enhanced CDT in vitro and in vivo. The system demonstrated a dual therapeutic effect: anti-tumor immunity and significant cancer pain relief by reducing HIF-1α and VEGF-A levels.Conclusion: The novel (Q+M/MnOx)@Clip system represents a promising advancement in nanomedicine, improving the bioavailability of quercetin and offering a more effective approach to cancer treatment by downregulation of HIF-1α and VEGF-A. This study demonstrates the potential for combining anti-tumor immunity with pain relief for triple-negative breast cancer therapy.Keywords: quercetin, pain relief, cancer immunotherapy, chemodynamic therapy, biomimetic, oxygen generation

Metal-organic frameworks (MOFs) with high porosity, specific surface area, and unique topologies are highly regarded for their applications in photocatalysis, medical treatment, and environmental pollutant degradation. However, due to the limitations of the tumor microenvironment (TME), traditional MOFs have limited efficacy in this environment. This paper designs multi-metal oxide-based heterostructure POMOFs nanoreactors with a nesting doll-like structure. This new structure not only exhibits therapeutic effects in TME but also utilizes ultrasound (US) to enhance the release of reactive oxygen species (ROS) for CDT&SDT co-therapy, becoming an effective sound sensitizer for destroying tumor cells. In summary, our study proposes an idea for constructing multi-metal oxide-based heterostructure MOFs nanoreactors material with a nesting doll-like structure to enhance ROS release and synergistically treat tumor diseases. [Display omitted]